pH-responsive alginate-hyaluronic acid microbeads produced via optimized electrospray method for oral ibuprofen delivery

Encapsulating active compounds in alginate–hyaluronic acid (ALG–HA) microbeads provides a biocompatible, calcium-cross-linkable platform for oral nonsteroidal anti-inflammatory drug delivery with the potential to minimize gastric drug release and promote intestinal release. To address the challenge of achieving uniformly spherical beads with narrow size distributions, we used electrospraying to generate ALG–HA droplets and subsequently ionotropically cross-linked them using calcium chloride. Bead size and morphology were characterized, rheology of pre-gel polymer solutions was assessed, and ibuprofen encapsulation and release were evaluated in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The process yielded spherical microbeads with a narrow size distribution and consistent morphology, exhibiting mean diameters of 2456 ± 146 μm and 638 ± 170 μm, with PDI values ranging from 0.0035 to 0.0706. Ibuprofen release remained low in SGF and increased in SIF, demonstrating pH-responsive release behaviour. Electrosprayed, calcium cross-linked ALG–HA microbeads therefore constitute a promising platform for the oral delivery of ibuprofen, with potential for minimizing gastric drug release and promoting intestinal release. To our knowledge, this is the first assessment of electrosprayed, calcium cross-linked ALG–HA microbeads for pH-responsive ibuprofen delivery.